Changes in the Use of Montelukast for Asthma After a US Food and Drug Administration Boxed Warning

Shanmugam H, Kesselheim AS, Liu ITT et al. JAMA Netw Open. 2026;9(5):e2614274. doi:10.1001/jamanetworkopen.2026.14274

Key Points

• Question  Did the use of montelukast to treat asthma change after an US Food and Drug Administration (FDA) boxed warning was announced in March 2020?
• Findings  In this cross-sectional study using national monthly cohorts of up to 614 637 patients with asthma from a national commercial claims dataset, the use of montelukast decreased after implementation of an FDA boxed warning.
• Meaning  These findings suggest that treatment patterns for patients with asthma changed after an FDA boxed warning.

Abstract

Importance  In March 2020, the US Food and Drug Administration (FDA) issued a boxed warning for montelukast amid reports of neuropsychiatric adverse effects.

Objective  To determine whether a boxed warning for montelukast was associated with changes in prescription rates of montelukast to treat asthma in the US.

Design, Setting, and Participants  In this serial cross-sectional study using a national commercial insurance claims database, monthly cohorts of individuals aged 6 years and older with an asthma diagnosis and continuous insurance coverage in the past year were created from October 2017 to December 2022. Results were stratified by age group, inhaled corticosteroid (ICS) use, and 1 or more asthma-related emergency department visit or hospitalization in the prior year. Data were analyzed from August 2024 to June 2025.

Exposures  Announcement of a boxed warning for montelukast in March 2020.

Main Outcomes and Measures  Monthly incidence and prevalence of montelukast use among patients with asthma. Data were analyzed with an interrupted time series analysis using segmented ordinary least-squares linear regression models with Newey-West standard errors.

Line Graph of Montelukast Use Before and After
March 2020 Boxed Warning

Results  The number of patients with asthma ranged from 594 253 in October 2017 to 614 637 in December 2022. In October 2017, 348 359 patients (58.6%) were female, 113 913 (19.2%) were younger than age of 18 years, 292 730 (49.3%) used an ICS, and 105 869 (17.8%) had 1 or more asthma-related emergency department visit or hospitalization in the prior year. The baseline monthly prevalence of montelukast use was 160.0 per 1000 patients with asthma, and the baseline incidence of new montelukast use was 5.8 per 1000. After the boxed warning, the level of monthly incident montelukast prescriptions decreased by 1.7 (95% CI, −2.2 to −1.3) per 1000 and the trend in montelukast prevalence decreased by 0.9 (95% CI, −1.1 to −0.6) per 1000 per month relative to the prewarning trend. The trend in prevalent montelukast use decreased after the boxed warning across all age and asthma severity subgroups.

Conclusions and relevance  In this cross-sectional study of commercially insured patients with asthma, an FDA boxed warning for montelukast was associated with changes in asthma treatment use among patients of all ages.

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